Dr. Susan O'Brien: My Reflections on ASH 2015

Published on
February 2, 2016

Topics include:
Treatment

On location
at the American Society of Hematology (ASH) 2015
meeting, Dr. Susan O’Brien of the University of California, Irvine, answers
several questions about frontline treatment for patients at different stages of
CLL. Dr. O’Brien discusses treatment for
relapsed-refractory patients, toxicity concerns and 17p deletion, as well as
shares her excitement for possible FDA approval by 2017 for rituximab (Rituxan)
in combination treatments.

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Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

So the approach to newly diagnosed CLL has not
yet changed that much with the exception of the fact that patients with 17P
deletion, who are a small subset, about 5 to 10 percent of newly diagnosed
patients who need treatment, have a very poor prognosis with chemotherapy, and
we now have ibrutinib (Imbruvica), the BTK inhibitor which has been approved
for only that subset as frontline therapy.

That being said, I think that’s about to change very quickly
and that’s because we heard of this meeting and it recently was published
online in “The New England Journal of Medicine” about the randomized trial in
newly diagnosed patients over the age of 65 who are requiring therapy. And they
were randomized to receive either chlorambucil (Leukeran), the alkylating agent,
or ibrutinib and that trial showed that ibrutinib was much more powerful
resulting in responses, progression-free survival and overall survival.

So we have the expectation that early in 2016 that will be
approved at least for the older patient subset, and we’re not sure yet how wide
that label will be.

Question:

What about your approach to treating relapsed and
refractory CLL patients?

Dr. O’Brien:

So where our treatments have changed is in relapsed-refractory
population because historically every treatment we had was chemotherapy based.

Now, we have two novel BCR inhibitors, BCR receptor
inhibitors that have been approved for treatment of relapse CLL. Ibrutinib, the BTK inhibitor, and idelalisib
(Zydelig), which is a PI3K?delta inhibitor and was approved in combination with
rituximab (Rituxan), and we have either of those options for relapse. Generally, after a patient receives chemo in
relapses now, I would not use chemotherapy again; I would go to one of those
two agents.

Question:

The drug idelalisib has been approved in
combination with rituximab for relapsed CLL/SLL patients. What is your experience with this
combination?

Dr. O’Brien:

So the combination of idelalisib and rituximab in
frontline patients, and it was used in patients over the age of 65, proved to
be highly successful in producing responses and long-term progression-free
survival. However, there was some toxicity associated with it. Some of the things we were already aware of,
we see transaminitis which is not a big deal.
We just monitor for it. And if we see it go to grade 3 to 4, we
just hold the drug and then resume it later on.

One of the more serious complications is pneumonitis. It’s
probably only about 5 percent of patients, but it’s important to recognize
it because you may be thinking the patient has pneumonia whereas if you’re
thinking it’s possibly pneumonitis, you want to give them steroids. And the third complication that we saw more
of in the frontline population was colitis.
I think in retrospect, because it’s a very late toxicity, we probably
didn’t recognize it very early.

I think now that people are aware of it, if you have a
patient with late diarrhea, you know, sometimes after they’ve been on the drug
for a year, what you need to do as you’re gonna begin your workup for the
diarrhea is to hold the drug, and that’s important and something we didn’t do
at a time where we weren’t thinking that the drug was causing the diarrhea say
15 months into the therapy. So I
think now that people are aware of it, and by the way there is a white paper
that’s been published on how to deal with the colitis, I think that will become
a less significant problem going forward.

Question:

What in particular has excited you at ASH 2015?

Dr. O’Brien:

I think one of the things that are very exciting
is venetoclax. That’s the Bcl?2
inhibitor. It’s another oral agent, non?chemotherapy,
and that’s produced some very good responses in patients with 17p deletion and
very high resubsa.

But also in other patients with relapse disease and an
update in terms of a combination with rituximab was presented and it looks like
not only do you get higher response rates but now we start to see a significant
number of complete remissions in relapse and some of those remissions are even
MRD negative, which is highly impressive in a relapse population, so I think
there’s a lot of excitement about that drug, and I think you will see it FDA
approved early in the coming year.

Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That’s how you’ll get care that’s most appropriate for you.

At the ASH 2015 meeting, CLL expert Dr. Jan Burger discussed the results from the RESONATE-2 trial, which studied the use of ibrutinib (Imbruvica) vs. chlorambucil in the frontline setting in patients over 65.